A scanning mobility particle sizer (SMPS) allows size separation of ga
s phase particles according to their electrophoretic mobilities. The a
ddition of an electrospray source (ES) recently allowed extension of S
MPS analysis to the macromolecular range. We demonstrate here the appl
ication of ES-SMPS to nucleic acids analysis. Single- and double-stran
ded DNA molecules ranging from 6.1 kDa (single-stranded DNA 20 nucleot
ides in length) to 300 kDa (500 base-pair double-stranded DNA) were se
parated and detected by ES-SMPS at the picomole to femtomole levels. T
he measured electrophoretic mobility diameters were found to correlate
with the analytes' molecular weights, while the peak areas could yiel
d quantitative information. No fragmentation of DNA was observed under
the conditions employed. Different apparent densities were observed f
or single-stranded and double-stranded DNAs, showing a different behav
ior for each type of biomolecule. The total analysis time was about 3
min/spectrum. Further optimization of ES-SMPS is expected to make it a
fast and sensitive technique for biopolymer characterization.